The long-term objective of this project is to gain a more thorough understanding of the autonomic neural control of cardiac function. The characteristic pattern of activity in efferent cardiac vagal fibers consists of a burst of action potentials each cardiac cycle. The specific aims of the proposed experiments are (1) to determine the cardiac effects of changes in the temporal pattern of such bursts of efferent vagal activity, (2) to determine the extent of convergence of preganglionic axons from the right and left vagus nerves on the postganglionic parasympathetic neurons in the intracardiac ganglia, and (3) to determine the synchronizing effects of repetitive bursts of vagal activity on the individual components of a putative multicentric right atrial pacemaker complex. Most of the studies will be carried out in open-chest, anesthetized dogs. A computer will control the number of pulses in each stimulus burst, the time between individual pulses in each burst, and the time of each burst within each cardiac cycle. The extent of "facilitation" of neurotransmission will be assessed by comparing the overall responses to stimulus bursts with different numbers of pulses. Similar studies will also be carried out in isolated, vagally innervated chicken hearts. During vagal stimulation, easily detectable quantities of acetylcholine (ACh) overflow from the isolated chicken heart. Such experiments will enable us to correlate the mechanical behavior of the heart with the overflow of ACh as the characteristics of the vagal stimulus bursts are altered. In the studies on synchronization of the multicentric pacemaker complex, an array of 180 electrodes applied to the external surface of the right atrium of anesthetized dogs will permit the generation of activation sequence and potential distribution maps. From such maps the effects of changes in the characteristics of the vagal stimulus bursts on the initiation and coordination of cardiac excitation can be determined.